RESUMO
Blood transfusions save lives and improve health every day. Despite the matching of blood types being stricter than it ever has been, emergency transfusions among incompatible blood types are still inevitable in the clinic when there is a lack of acceptable blood types for recipients. Here to overcome this, a counter measure nanoplatform consisting of a polymeric core coated by a red blood cell (RBC) membrane is developed. With A-type or B-type RBC membrane camouflaging, the nanoplatform is capable of specifically capturing anti-A or anti-B IgM antibodies within B-type or A-type whole blood, thereby decreasing the corresponding IgM antibody levels and then allowing the incompatible blood transfusions. In addition to IgM, the anti-RBC IgG antibody in a passive immunization murine model can likewise be neutralized by this nanoplatform, leading to prolonged circulation time of incompatible donor RBCs. Noteworthily, nanoplatform made by expired RBCs (>42 days stored hypothermically) and then subjected to lyophilization does not impair their effect on antibody neutralization. Most importantly, antibody-captured RBC-NP do not exacerbate the risk of inflammation, complement activation, and coagulopathy in an acute hemorrhagic shock murine model. Overall, this biomimetic nanoplatform can safely neutralize the antibody to enable incompatible blood transfusion.
Assuntos
Membrana Eritrocítica , Nanopartículas , Animais , Camundongos , Membrana Eritrocítica/imunologia , Transfusão de Sangue/métodos , Modelos Animais de Doenças , Humanos , Eritrócitos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologiaRESUMO
Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.
Assuntos
Candida albicans , Candidíase Vulvovaginal , Células Epiteliais , Humanos , Animais , Camundongos , Células Cultivadas , Candidíase Vulvovaginal/terapia , Fototerapia , Fármacos Fotossensibilizantes/farmacologiaRESUMO
With its well-documented toxicity, the use of doxorubicin (Dox) for cancer treatment requires trade-offs between safety and effectiveness. This limited use of Dox also hinders its functionality as an immunogenic cell death inducer, thus impeding its usefulness for immunotherapeutic applications. Here, we develop a biomimetic pseudonucleus nanoparticle (BPN-KP) by enclosing GC-rich DNA within erythrocyte membrane modified with a peptide to selectively target healthy tissue. By localizing treatment to organs susceptible to Dox-mediated toxicity, BPN-KP acts as a decoy that prevents the drug from intercalating into the nuclei of healthy cells. This results in significantly increased tolerance to Dox, thereby enabling the delivery of high drug doses into tumor tissue without detectable toxicity. By lessening the leukodepletive effects normally associated with chemotherapy, dramatic immune activation within the tumor microenvironment was also observed after treatment. In three different murine tumor models, high-dose Dox with BPN-KP pretreatment resulted in significantly prolonged survival, particularly when combined with immune checkpoint blockade therapy. Overall, this study demonstrates how targeted detoxification using biomimetic nanotechnology can help to unlock the full potential of traditional chemotherapeutics.
Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Animais , Camundongos , Doxorrubicina , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Microambiente TumoralRESUMO
The pharmacological activities of dictamnine and fraxinellone have been well reported; however, only a few studies have focused on the pharmacokinetics and bioavailability of concomitant delivery of these drugs in vivo. To shed light on this neglected area, we developed a rapid and sensitive UPLC-MS/MS method that quantified the levels of dictamnine and fraxinellone simultaneously in rat plasma. This method was initiated by a one-step protein precipitation strategy to purify plasma samples collected from rats treated with either oral or intravenous administration of dictamnine and fraxinellone. The mobile phase contained acetonitrile and 0.1% formic acid at a steady flow rate of 0.6 mL/min. As a result, an excellent analyte peak resolution was achieved, and the entire process took only 3 min per sample. The results were indicative of the desired linearity (r2 ≥ 0.999), precision (RSD% was within 15%), accuracy (RE% was within 15%), recoveries (≥80.66 and 68.15% for dictamnine and fraxinellone, respectively) and matrix effects (≥94.66 and 91.37% for dictamnine and fraxinellone, respectively). Additionally, the detectable limits of these two compounds were both low even when they reached 5 ng/mL. Taken together, these findings contribute to a better understanding of the pharmacokinetics and bioavailability properties of concomitant delivery of dictamnine and fraxinellone.
Assuntos
Espectrometria de Massas em Tandem , Ratos , Animais , Disponibilidade Biológica , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Administração Intravenosa , Administração Oral , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Based on graphite-like carbon nitride (g-CN) nanocomposites coupled with aptamer, a regenerable electrochemiluminescence (ECL) biosensor is developed for the quantitative detection of aflatoxin B1 (AFB1). In the existence of AFB1, the structure of the aptamer changed into a loop, and the original ECL intensity was reduced owing to the enhancement of luminescence quenching between the ferrocene modified at the end of the aptamer and the luminescent substrate g-CN. Moreover, AFB1 with oxidation state could also react with high energy state g-CN, leading to further reduction of the electrochemiluminescence signal. At optimum conditions, ECL intensity was decreased in linearity with an AFB1 concentration range from 0.005 ng/mL to 10 ng/mL, and the minimum detectable concentration was down to 0.005 ng/mL, which realized trace detection demand with high sensitivity. It was selective for AFB1 and its performance had been verified on rice samples, which indicated a promising applying prospect of non-enzymatic electrochemiluminescence AFB1 detection.
Assuntos
Técnicas Biossensoriais , Grafite , Grafite/química , Luminescência , Técnicas Biossensoriais/métodos , Aflatoxina B1/análise , Limite de Detecção , Medições Luminescentes/métodos , Técnicas EletroquímicasRESUMO
Purpose: Poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with the membrane of red blood cells (RBC-NP) have been applied in various biomedical fields. Despite the well-documented great biocompatibility, the potential toxicity of RBC-NP on maternal mice or their developing fetuses during pregnancy, or juvenile mice post-birth, remains unclear, which warrants a systematic evaluation. Methods: We fabricate an RBC-NP with approximately 50 nm in diameter (RBC-NP-50). Upon RBC-NP-50, pregnant mice are intravenously injected with this nanoparticle either at a single high dose of 400 mg/kg (1HD) or a low dose of 200 mg/kg for 3 times (3LD). Afterwards, the biocompatible assessments are performed at 48 h after the final injection or 21 d post-birth/partum both on maternal and fetal/juvenile mice. Results: RBC-NP-50 is capable of accumulating in the placenta and then passing through the blood-fetal barrier (BFB) into the fetus. On 48 h after RBC-NP-50 exposure, no significant dose-dependent toxicity is observed in maternal mice including blood biochemistry, inflammatory factors, progesterone level, histological analysis, etc, whereas fetal brains reveal remarkable differentially expressed genes analyzed by transcriptome sequencing. On 21 d post-birth, those genes' expression in juvenile mice is alleviated, along with negligible differences in behavioral evaluations including surface righting test, negative geotaxis test, cliff avoidance test, and olfactory orientation test. Conclusion: These results indicate that RBC-NP is considered to be generally safe and biocompatible both for maternal mice and fetus during pregnancy, and for the subsequent juvenile mice post-birth, although future studies will need to examine higher dosage or longer-term measurements.
Assuntos
Membrana Eritrocítica , Camundongos , AnimaisRESUMO
With few options available for the effective treatment of multidrug-resistant bacteria, photodynamic therapy (PDT) has emerged as a promising therapeutic strategy that does not promote the development of antibiotic resistance. Unfortunately, the beneficial bactericidal effect of PDT is oftentimes accompanied by the uncontrollable production of reactive oxygen species. To overcome this issue, a pore-forming toxin (PFT)-responsive biomimetic nanobubble is designed, which is constructed by co-encapsulating a perfluorocarbon nanoemulsion and a photosensitizer within the red blood cell membrane. It is shown that PFTs derived from three pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), group A Streptococcus (GAS), and Listeria monocytogenes (LM), can be effectively absorbed by the nanobubble. Upon toxin absorption, the formation of pores on the nanobubble surface allows the accelerated release of oxygen dissolved inside the nanoemulsion along with the photosensitizer, thus resulting in enhanced PDT and bactericidal efficacy. In three skin infection models, treatment with the nanobubbles results in significantly decreased lesion formation and reduced inflammation. In addition to oxygen, the platform can be used to deliver nitric oxide in a bacterial toxin-dependent manner. Overall, biomimetic nanobubbles may work as a broad gas delivery system that is capable of responding to a variety of PFT-based stimuli for precision PDT.
Assuntos
Infecções Bacterianas , Toxinas Bacterianas , Fluorocarbonos , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Antibacterianos/farmacologia , Biomimética , Humanos , Óxido Nítrico/farmacologia , Oxigênio/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismoRESUMO
An effective therapeutic strategy against methicillin-resistant Staphylococcus aureus (MRSA) that does not promote further drug resistance is highly desirable. While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off-target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore-forming toxins trigger on-demand payload release. Upon subsequent near-infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on-demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high-priority pathogens.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Lipossomos/farmacologia , Testes de Sensibilidade Microbiana , Fototerapia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/prevenção & controleRESUMO
BACKGROUND: Our previous studies suggest that human fat extract (FE) contains a variety of angiogenic factors and may provide an alternative treatment option for stroke. However, the therapeutic effect is largely limited due to its short half-life, and inaccurate targeting. RESULTS: Herein, we leverage the targeting abilities of platelets (PLTs) to the lesion area of stroke and Arg-Gly-Asp (RGD) peptides to the angiogenic blood vessels to develop a biomimetic nanocarrier that capable of delivering FE precisely to treat stroke. The biomimetic nanocarriers are comprised of FE-encapsulated PLGA (poly(lactic-co-glycolic acid)) core enclosed by RGD peptides decorated plasma membrane of PLTs, namely RGD-PLT@PLGA-FE. We found that RGD-PLT@PLGA-FE not only targeted damaged and inflamed blood vessels but also achieved rapid accumulation in the lesion area of ischemic brain. In addition, RGD-PLT@PLGA-FE kept a sustained release behavior of FE at the lesion site, effectively increased its half-life and promoted angiogenesis and neurogenesis with delivering neurotrophic factors including BDNF, GDNF and bFGF to the brain, that ultimately resulted in blood flow increase and neurobehavioral recovery. CONCLUSIONS: In conclusion, our study provides a new strategy to design a biomimetic system for FE delivery and it is a promising modality for stroke therapy.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Plaquetas , Sistemas de Liberação de Medicamentos , Humanos , AVC Isquêmico/tratamento farmacológico , Peptídeos , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
Hybrid metal compounds have been paid increasing attention for the development of electroanalysis materials due to the specific collaboration interaction and synergy effect of metal elements. Herein, a series of ultrathin Ni/Co bimetallic metal-organic-framework nanosheets (UMOFNs) with different metal ratios were investigated as high-performance electroanalysis materials for non-enzymatic glucose electrochemical sensing. The synergistic effect between Ni/Co endowed UMOFNs with not only the unique electrochemical behavior that prompts the sensing-related electrochemical oxidation at a low applied potential, but also the enhanced affinity to glucose; also, they facilitated the electron transfer involving the analyte. The UMOFN composite with an elaborately adjusted Co/Ni ratio exhibits an extremely outstanding glucose sensing performance, including high sensitivity (2086.7 µA mM-1 cm-2), wide linear range (0.1 µM-1.4 mM), low detection limit (0.047 µM), and excellent selectivity. It can also be used for the detection of glucose in actual human serum samples with an accuracy of 90.1%, demonstrating a good application prospect of the non-enzymatic electrochemical glucose detection.
Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Glucose/análise , Estruturas Metalorgânicas/química , Nanopartículas/química , Cobalto/química , Teoria da Densidade Funcional , Eletrodos , Humanos , Teste de Materiais , Estruturas Metalorgânicas/síntese química , Níquel/química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
With the rise of bacterial infections and antimicrobial resistance, it is important to develop environmentally friendly functional materials and surfaces with efficient bactericidal activity. In this work, nanostructured graphitic carbon nitride (g-C3N4) surfaces were fabricated by electrophoresis deposition of mesoporous g-C3N4 materials. Efficient bactericidal performance was achieved through the synergistic biophysical interaction of bacterial cells with the nanotopographies and visible light active photocatalytic properties. The nanotopographies of g-C3N4 surfaces demonstrated a "contact-killing" efficiency of >90% against Pseudomonas aeruginosa and >80% against Staphylococcus aureus cells. The number of surviving bacteria on the surfaces further decreased remarkably upon illumination using visible light generated by a light-emitting diode lamp with an irradiation intensity of 12.4 mW cm-2. In total, the number of viable bacteria was reduced by approximately 3 orders of magnitude for P. aeruginosa and 2 orders of magnitude for S. aureus. Our experimental findings provide potential prospects for developing highly efficient photocatalytic bactericidal surfaces.